End-stage renal disease (ESRD) is associated with a markedly reduced patient survival and substantial morbidity. The life expectancy of a 40 year-old dialysis patient is 8.8 years, as compared with 37.4 years for the general U.S. population of the same age. Retrospective studies have suggested that higher Kt/V and use of dialysis membranes with higher flux and greater biocompatibility may decrease morbidity and mortality in maintenance hemodialysis patients, but few prospective studies have evaluated the effects of such manipulations. This prospective, randomized, multicenter investigation will test the following hypotheses: (1) Hemodialysis achieving higher Kt/V results in decreased mortality in ESRD patients undergoing maintenance hemodialysis. (2) Hemodialysis with membranes of higher flux decreases mortality and morbidity. (3) These two interventions are safe and acceptable to hemodialysis patients. In-center hemodialysis patients will be randomized to receive dialysis treatments with either standard or high Kt/V (1.0 vs 1.4, double pool) and using either high flux membranes or low flux membranes. Subjects will be randomized to one of four experimental groups: a. Kt/V 1.40; High flux membrane b. Kt/V 1.40; Low flux membrane c. Kt/V 1.00; High flux membrane d. Kt/V 1.00; Low flux membrane All other aspects of the patients' medical and dialysis care will follow the usual standards of care. The study subjects will be followed prospectively for five years to determine: a. Patient mortality (primary endpoint) b. Patient morbidity (secondary endpoint) i. Non-access related hospitalization (especially cardiovascular events or serious infections) ii. Malnutrition (a decline in serum albumin) The results will be analyzed to determine whether there are significant differences in patient survival or morbidity among the four treatment groups.